Butyrylcholinesterase



Butyrylcholinesterase (BChE) is an enzyme widely distributed throughout the body in humans, but particularly prevalent in serum, where it occurs as a tetramer of catalytic subunits. It is distinguished from the homologous enzyme, acetylcholinesterase, by its ability to hydrolyze the non-natural substrate butyrylcholine as well as the neurotransmitter, acetylcholine. Its biological role remains obscure, but mutations in the human BCHE gene result in prolonged post-surgical apnea due to the inability of the mutant BChEs to hydrolyse the local anaesthetic, succinylcholine. BChE finds medical use as a bioscavenger for overcoming organophosphate (OP) nerve agent and insecticide intoxication by interacting rapidly with the toxic agents. Crystal structures of both the native enzyme and of its conjugates with nerve agents are available. The image at the right correspond to one representative BChE, i.e. the crystal structure of recombinant full length human butyrylcholinesterase (2pm8).

hBChE - Apo human
2pm8, 1p0i - hBChE - human

2xmb – hBChE (mutant)+SO4

2xmc - hBChE (mutant)+F

BChE+OP irreversible inhibitors, including nerve agents and insecticides
3djy, 3dkk - hBChE+tabun

2wid, 2wif - hBChE+Tabun analogue TA1

2wsl, 2wig – hBChE+Tabun analogue TA4

2wil, 2wij - hBChE+Tabun analogue TA5

2wik - hBChE+Tabun analogue TA6

1xlw - hBChE+echothiophate

1xmd, 2xmd – hBChE (mutant)+echothiophate

1p0q - hBChE+soman

1xlu - hBChE+Di-Isopropyl-Phosphoro-Fluoridate (DFP)

2xmg - hBChE (mutant)+VX

1xlv – hBChE+ethyl dihydrogen phosphate

BChE+inhibitor binding at surface of the protein (far from the active site)
2j4c – hBChE+ HgCl2

BChE + substrate analogues mimicking the binding of the substrate butyrylcholine
1p0m - hBChE+choline

1p0p - hBChE+butyrylthiocholine

Additional Resources
For additional information, see: Alzheimer's Disease